MicroPET investigation of chronic long-term neurotoxicity from heavy ion irradiation

Abstract

Positron emission tomography (PET) permits imaging of the regional biodistribution and pharmacokinetics of compounds labeled with short-lived positron-emitting isotopes. It has enabled evaluation of neurochemical systems in the living human brain, including effects of toxic substances. MicroPET devices allow studies of the rat brain with a spatial resolution of approximately 2 mm. This is much poorer resolution than obtained using ex vivo autoradiography. However, animals need not be euthanized before imaging, so repeat studies are possible. This in principle allows the effects of toxic insults to be followed over the lifetime of an individual animal. We used microPET to evaluate brain metabolic effects of irradiation with high-energy heavy ions (HZE radiation), a component of the space radiation environment, on regional glucose metabolism. A significant fraction of neurons would be traversed by these densely ionizing particles during a Mars mission, and there is a need to estimate human neurological risks of prolonged voyages beyond the geomagnetosphere. Rats were irradiated with 56Fe (600 MeV/n) ions at doses up to 240 cGy. At 9 months post-irradiation we did not detect alterations in regional accumulation of the glucose analog [18F]2-deoxy-2-fluoro-D-glucose. This may indicate that damage to the brain from HZE particles is less severe than feared. However, because radiation-induced alterations in some behaviors have been documented, it may reflect insensitivity of baseline cerebral glucose metabolism to HZE radiation. These studies will facilitate design of future studies of chronic, long-term exposure to both therapeutic and abused drugs using microPET.